TNBS誘起ラット大腸炎における温度感受性TRPV2およびTRPV1の免疫組織学的解析と内臓痛覚過敏への関与

• Published in: 日本薬理学会年会要旨集 p. 3-B-P-250
• Main Authors: 加藤, 伸一, 松本, 健次郎, 安田, 浩之, 宮本, 早也佳
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2022
• Subjects: colon; neuropeptide; pain; sensory neuron
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.96.0_3-B-P-250

TRPV2 and TRPV1 are originally identified as heat sensitive TRP channels. We investigated the expression patterns of TRPV2 and TRPV1 in the rat distal colon and extrinsic primary afferent neurons, and their roles in visceral hypersensitivity in TNBS-induced colitis rats. Both TRPV2 and TRPV1 expressions in colon, DRG, and nodose ganglion (NG) were significantly upregulated in TNBS-induced colitis. TRPV2-expressing cell bodies colocalized with the intrinsic primary afferent marker NeuN and the inhibitory motor neuronal marker nNOS in myenteric plexus. TRPV2 expressions also colocalized with the resident macrophage marker ED2 in the mucosa while no TRPV1-expressing cell bodies were detected in the myenteric plexus. Both TRPV2- and TRPV1-expressing cell bodies in DRG and NG were double-labeled with the neuronal retrograde tracer fluorescent fluorogold. Large- and medium-sized TRPV2-positive neurons were labeled with the A-fiber marker NF200, CGRP, and substance P in DRG while small-sized TRPV1-positive neurons were labeled with the C-fiber markers IB4, CGRP, and substance P. TRPV2- and TRPV1-positive NG neurons were2 / 2labeled with NF200 and IB4. TNBS treatment increased p-ERK1/2-positive cells in TRPV2 and TRPV1 neurons but did not affect the subpopulations in the DRG and NG. Both TRPV2 and TRPV1 antagonists significantly alleviated visceral hypersensitivity in TNBS-induced colitis model rats. These findings suggest that intrinsic/extrinsic TRPV2- and extrinsic TRPV1-neurons contribute to visceral hypersensitivity in an experimental colitis.